Central nervous system (CNS) involvement is often a critical and even life-threatening occurrence in systemic lupus erythematosus (SLE). Much documentation exists on the causal relationship between immune complexes and the pathogenesis of glomerulonephritis and vasculitis in SLE. There is evidence to suggest that immune complexes also have an important role in the pathogenesis of CNS dysfunction. Complex deposition in the choroid plexus, an organ with functional and structural similarities to the glomerulus, may set off a biological cascade of events resulting in organic and functional CNS disturbances. Furthermore, damage to the blood-brain barrier possibly by immune complex-mediated changes in the choroid plexus and/or the CNS vasculature may allow autoantibodies to brain tissue to interfere with normal CNS functioning. The purpose of the proposed investigation will be to focus on the underlying pathogenic mechanisms responsible for the CNS manifestations of SLE. An interdisciplinary approach will be taken in which immunological, neurophysiological, and behavioral parameters will be followed in both natural and experimentally induced immune complex diseases of laboratory animals. NZB/W mice will be used as a natural model while rabbits and rats will be used as experimental models of immune complex disease. An attempt will be made to determine if NZB/W mice manifest spontaneous abnormalities of CNS functin as measured by behavioral and electrophysiological techniques. The role of immune complexes and other possible immunologic factors in mediation of the CNS abnormalities and phenomena relating to the development of immune complex disease and in normal animals in order to determine the specific effects of immune complexes and antibodies to thymocytes on the central nervous system.